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BACKGROUND: Biomarkers for idiopathic inflammatory myopathies are difficult to identify and may involve expensive laboratory tests. We assess the potential for artificial intelligence (AI) to differentiate children with juvenile dermatomyositis (JDM) from healthy controls using nailfold capillaroscopy (NFC) images. We also assessed the potential of NFC images to reflect the range of disease activity with JDM. METHODS: A total of 1,120 NFC images from 111 children with active JDM, diagnosed between 1990 and 2020, and 321 NFC images from 31 healthy controls were retrieved from the CureJM JDM Registry. We built a lightweight and explainable deep neural network model called NFC-Net. Images were downscaled by interpolation techniques to reduce the computational cost. RESULTS: NFC-Net achieved high performance in differentiating patients with JDM from controls, with an area under the ROC curve (AUROC) of 0.93 (0.84, 0.99) and accuracy of 0.91 (0.82, 0.92). With sensitivity (0.85) and specificity (0.90) resulted in model precision of 0.95. The AUROC and accuracy for predicting clinical disease activity from inactivity were 0.75 (0.61, 0.81) and 0.74 (0.65, 0.79). CONCLUSION: The good performance of the NFC-Net demonstrates that NFC images are sufficient for detecting often unrecognized JDM disease activity, providing a reliable indicator of disease status. IMPACT: Proposed NFC-Net can accurately predict children with JDM from healthy controls using nailfold capillaroscopy (NFC) images. Additionally, it predicts the scores to JDM disease activity versus no activity. Equipped with gradients, NFC-Net is explainable and gives visual information beside the reported accuracies. NFC-Net is computationally efficient since it is applied to substantially downscaled NFC images. Furthermore, the model can be wrapped within an edge-based device like a mobile application that is accessible to both clinicians and patients.
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Dermatomiositis , Niño , Humanos , Dermatomiositis/diagnóstico , Angioscopía Microscópica/métodos , Inteligencia Artificial , BiomarcadoresRESUMEN
OBJECTIVE: This study determined if an accessible, serologic indicator of vascular disease activity, the von Willebrand factor antigen (vWF:Ag), was useful to assess disease activity in children with juvenile dermatomyositis (JDM), a rare disease, but the most common of the pediatric inflammatory myopathies. METHODS: A total of 305 children, median age 10 years, 72.5% female, 76.5% white, with definite/probable JDM at diagnosis, were enrolled in the Ann & Robert H. Lurie Cure JM Juvenile Myositis Repository, a longitudinal database. Disease Activity Score (DAS) and vWF:Ag data were obtained at each visit. These data were analyzed using generalized estimating equation (GEE) models (both linear and logistic) to determine if vWF:Ag reflects disease severity in children with JDM. A secondary analysis was performed for untreated active JDM to exclude the effect of medications on vWF:Ag. RESULT: The vWF:Ag test was elevated in 25% of untreated JDM. We found that patients with elevated vWF:Ag had a 2.55-fold higher DAS total (CI95: 1.83-3.27, p < 0.001). Patients with difficulty swallowing had 2.57 higher odds of elevated vWF:Ag (CI95: 1.5-4.38, p < 0.001); those with more generalized skin involvement had 2.58-fold higher odds of elevated vWF:Ag (CI95: 1.27-5.23, p = 0.006); and those with eyelid peripheral blood vessel dilation had 1.32-fold higher odds of elevated vWF:Ag (CI95: 1.01-1.72, p = 0.036). Untreated JDM with elevated vWF:Ag had more muscle weakness and higher muscle enzymes, neopterin and erythrocyte sedimentation rate compared to JDM patients with a normal vWF:Ag. CONCLUSION: vWF:Ag elevation is a widely accessible concomitant of active disease in 25% of JDM.
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Polycystins are conserved mechanosensitive channels whose mutations lead to the common human renal disorder autosomal dominant polycystic kidney disease (ADPKD). Previously, we discovered that the plasma membrane-localized fission yeast polycystin homolog Pkd2p is an essential protein required for cytokinesis; however, its role remains unclear. Here, we isolated a novel temperature-sensitive pkd2 mutant, pkd2-B42. Among the strong growth defects of this mutant, the most striking was that many mutant cells often lost a significant portion of their volume in just 5â min followed by a gradual recovery, a process that we termed 'deflation'. Unlike cell lysis, deflation did not result in plasma membrane rupture and occurred independently of cell cycle progression. The tip extension of pkd2-B42 cells was 80% slower than that of wild-type cells, and their turgor pressure was 50% lower. Both pkd2-B42 and the hypomorphic depletion mutant pkd2-81KD partially rescued mutants of the septation initiation network (SIN), a yeast Hippo-related signaling pathway, by preventing cell lysis, enhancing septum formation and doubling the number of Sid2p and Mob1p molecules at the spindle pole bodies. We conclude that Pkd2p promotes cell size expansion during interphase by regulating turgor pressure and antagonizes the SIN during cytokinesis. This article has an associated First Person interview with the first author of the paper.
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Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Transducción de Señal , Canales de Potencial de Receptor Transitorio , Ciclo Celular/fisiología , Humanos , Riñón Poliquístico Autosómico Dominante/genética , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Proteínas de Schizosaccharomyces pombe/metabolismo , Transducción de Señal/genética , Canales Catiónicos TRPP/genética , Canales Catiónicos TRPP/metabolismo , Canales de Potencial de Receptor Transitorio/genética , Canales de Potencial de Receptor Transitorio/metabolismoRESUMEN
BACKGROUND: Previous studies have assessed the prevalence and nature of traumatic injuries due to legal intervention in adults. The purpose of this study is to characterize and understand legal intervention trauma in children. METHODS: The National Trauma Data Bank (NTDB) was queried from 2007 to 2015. Patients (0-18 years old) who sustained injuries due to legal intervention were compared to those injured from other causes in the general NTDB population. Descriptive statistics were used to characterize the study population. Multivariate logistic regression models were utilized to predict firearm trauma and mortality. RESULTS: 622 patients sustained injuries involving legal intervention. Compared to general NTDB pediatric population, those who sustained legal intervention injuries were more likely to be older (age 16.5 vs. 10.6, p < 0.01), male (91.96% vs. 34.95%, p < 0.01), test positive for illegal drugs (64.64% vs. 38.35%, p < 0.01) or alcohol (26.36% vs. 17.25%, p < 0.01), and be African-American (44.37% vs. 17.00%, p < 0.01), Latino (22.82% vs. 15.10%, p < 0.01), or Native American (0.96% vs.. 0.94%, p < 0.01). Logistic regression models identified an 11% increased odds (95% CI 1.02-1.21, p = 0.02) of death among African-Americans when compared to other racial groups receiving legal intervention trauma. African-American status was associated with a 12% increased odds (95% CI 1.02-1.22, p = 0.01) of firearm trauma when compared to other racial groups receiving legal intervention trauma. CONCLUSION: Legal intervention-related pediatric trauma disproportionately affects the African-American population. This is particularly pronounced in cases of firearm related injuries. LEVEL OF EVIDENCE: III.
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Armas de Fuego , Heridas por Arma de Fuego , Adolescente , Adulto , Negro o Afroamericano , Niño , Preescolar , Hispánicos o Latinos , Humanos , Lactante , Recién Nacido , Masculino , Estudios RetrospectivosRESUMEN
Variations in cell wall composition and biomechanical properties can contribute to the cellular plasticity required during complex processes such as polarized growth and elongation in microbial cells. This study utilizes atomic force microscopy (AFM) to map the cell surface topography of fission yeast, Schizosaccharomyces pombe, at the pole regions and to characterize the biophysical properties within these regions under physiological, hydrated conditions. High-resolution images acquired from AFM topographic scanning reveal decreased surface roughness at the cell poles. Force extension curves acquired by nanoindentation probing with AFM cantilever tips under low applied force revealed increased cell wall deformation and decreased cellular stiffness (cellular spring constant) at cell poles (17 ± 4 mN/m) relative to the main body of the cell that is not undergoing growth and expansion (44 ± 10 mN/m). These findings suggest that the increased deformation and decreased stiffness at regions of polarized growth at fission yeast cell poles provide the plasticity necessary for cellular extension. This study provides a direct biophysical characterization of the S. pombe cell surface by AFM, and it provides a foundation for future investigation of how the surface topography and local nanomechanical properties vary during different cellular processes.